Current treatment options for repairing volumetric muscle loss injury involve the use of existing host tissue like muscular flaps or grafts. However, host muscle tissue may not be available and donor site morbidity, such as functional loss and volume deficiency, is often present. In this study, we developed a biofunctionalized muscle-derived decellularized extracellular matrix scaffolding system to utilize endogenous stem/progenitor cells for in situ muscle tissue regeneration. We optimized the decellularization process to enhance cellular infiltration and fabricated an insulin-like growth factor-binding protein 3 (IGFBP-3)-conjugated scaffold for controlled delivery of IGF-I. We then tested in vitro characterization including IGF-I release kinetics and cellular infiltration. In addition, we have analyzed the bioactivities of skeletal muscle cells (C2C12) to assess the indirect effect of released IGF-1 from the scaffold. The IGFBP-3 conjugated scaffolds demonstrated showed sustained release of IGF-1 and 1% SDS decellularized scaffold with IGF-1 showed higher cellular infiltration compared to control scaffolds (no conjugation). In indirect bioactivity assay, IGF-1 conjugated scaffold showed 2.1-fold increased cell activity compared to control (fresh media). Our results indicate that IGFBP-3/IGF-I conjugated scaffold has the potential to be used for in situ muscle tissue regeneration.
Preeclampsia is a syndrome with diverse clinical presentation that currently has no cure. The apelin receptor system is a pleiotropic pathway with a potential for therapeutic targeting in preeclampsia. We established the systemic outcomes of (Pyr
1
)-apelin-13 administration in rats with preeclamptic features (TGA-PE, female transgenic for human angiotensinogen mated to male transgenic for human renin). (Pyr
1
)-apelin-13 (2 mg/kg/day) or saline was infused in TGA-PE rats via osmotic minipumps starting at day 13 of gestation (GD). At GD20, TGA-PE rats had higher blood pressure, proteinuria, lower maternal and pup weights, lower pup number, renal injury, and a larger heart compared to a control group (pregnant Sprague-Dawley rats administered vehicle). (Pyr
1
)-apelin-13 did not affect maternal or fetal weights in TGA-PE. The administration of (Pyr
1
)-apelin-13 reduced blood pressure, and normalized heart rate variability and baroreflex sensitivity in TGA-PE rats compared to controls. (Pyr
1
)-apelin-13 increased ejection fraction in TGA-PE rats. (Pyr
1
)-apelin-13 normalized proteinuria in association with lower renal cortical collagen deposition, improved renal pathology and lower immunostaining of oxidative stress markers (4-HNE and NOX-4) in TGA-PE. This study demonstrates improved hemodynamic responses and renal injury without fetal toxicity following apelin administration suggesting a role for apelin in the regulation of maternal outcomes in preeclampsia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.